Neurosciences Commons^™

The Effect Of Cerebellar Transcranial Direct Current Stimulation On Anxiety, Shivangi Bhardwaj

All-Inclusive List of Electronic Theses and Dissertations

Anxiety is one of the most prevalent mental health disorders in the U.S. Individuals of all ages are affected by anxiety. Therefore, research into anxiety and its potential treatment has constantly been an area of interest. Newer approaches to managing anxiety include non-invasive stimulation techniques, such as Transcranial Direct Current Stimulation (tDCS), because of its accessibility and effectiveness. Past tDCS work typically focused on regions in the frontal lobe. However, tDCS over the cerebellum has not received as much attention compared to the cerebrum, despite recent work demonstrating cerebellar involvement in emotion processing. Thus, a better understanding of how cerebellar …

Engagement Of Understudied Populations As Community Change: The South Texas Adrc Model, Gladys E. Maestre, Neela K. Patel, Rosa V. Pirela, Robin C. Hilsabeck, Kendra Stine, Neyra García, Roberto Reyes, Omar Oropeza, Cristian Maestre, Jesus D. Melgarejo, Sarah Williams-Blangero, Ney Alliey Rodriguez

School of Medicine Publications

Many populations experiencing the highest burdens of Alzheimer's disease and related dementias remain understudied, in part because traditional recruitment and retention models are insufficient to support sustained engagement. The Outreach, Recruitment, and Engagement Core (OREC) of the South Texas Alzheimer's Disease Research Center reconceptualized participant recruitment as a long-term system change in a Hispanic-majority, urban–rural region. OREC institutionalizes shared power through community advisory governance, aligns research protocols with local lived realities (through patient navigators, community health workers/promotores, and decentralized access points), and employs a data-driven feedback loop for continuous improvement. In 1 year, 46 outreach events touched 10,134 individuals (71% …

Online Decoding Of Rat Self-Paced Locomotion Speed From Eeg Using Recurrent Neural Networks, Alejandro De Miguel, Nelson Totah, Uri Maoz

Psychology Faculty Articles and Research

Objective. Accurate and reliable neural decoding of locomotion holds promise for advancing clinical applications such as rehabilitation and prosthetic control, as well as for understanding neural correlates of action. Recent studies have demonstrated successful decoding of locomotion kinematics across species in motorized treadmill settings. However, efforts to decode locomotion speed directly and continuously in more natural contexts—where pace is self-selected rather than externally imposed—are scarce, and those that exist generally achieve only modest accuracy and require intracranial implants. Here, we aim to decode self-paced locomotion speed non-invasively and continuously using cortex-wide electroencephalography (EEG) recordings from rats. Approach. We introduce an …

Mapping The Neuroexposome: Integrative Analysis Of Dementia Risk Factors Through Multi-Omics And Environmental Profiling In The Egyptian Population., Mai Ahmed Saadzaghloul Othman

Theses and Dissertations

Background: Dementia represents one of the most pressing public health challenges of the twenty-first century, with the global burden projected to reach 153 million cases by 2050. Egypt, as the most populous Arab nation, faces a corresponding rise in age-related diseases, yet comprehensive data from low- and middle-income countries remain severely limited. The neuroexposome framework, integrating genetic susceptibility, environmental exposures, and metabolic alterations, offers a powerful strategy to characterize the complex interplay between internal and external risk factors for Alzheimer's disease (AD) and Alzheimer's disease Related Dementias (ADRD).

Objectives: This thesis aimed to: (1) examine the distribution of APOE alleles …

Decentralizing Dementia Research To The Us–Mexico Border: The Rio Grande Valley Ad-Rcmar As A Model For Translational Equity, Gladys E. Maestre, John Blangero, Eron Manusov, Gabriel A. De Erausquin, Francisco Fernandez, Silvia Mejia-Arango, Vincent P. Diego, Juan C. Lopez-Alvarenga, Claudia Alaniz, Neyra García, Rosa V. Pirela, Andrew Tsin, Michael Mahaney

School of Medicine Publications

Translational equity means ensuring that diagnostics, treatments, care models, and prevention strategies are developed and implemented so they work for populations with the greatest burden and least access to care. In Alzheimer's disease and related dementias (ADRD), where most evidence derives from highly educated, non-Hispanic White participants at large academic centers, translational equity is critical to prevent misclassification, limited access, and widening disparities and to ensure that underrepresented communities shape how new knowledge moves into practice. Hispanic and other populations in the United States are disproportionately affected by ADRD yet remain underrepresented in research, with gaps especially pronounced in high-poverty …

Foveate, Dahlia Aggarwal

Masters Theses

This thesis investigates how textiles can unsettle visual assumptions, encouraging a perceptual shift. Through weaving, upholstery, and spatial installation, the work stages a tension between what a surface appears to be and how it is encountered by the body. Through woven pattern, tactile texture, and trompe l’oeil textile surfaces, perception is something negotiated rather than fixed: the eye anticipates one reality while the hand discovers another.

Drawing on a range of sensations gathered from observing landscape formations and textures, it translates enduring scale and material qualities into an interior landscape of woven surfaces and textile-based furniture. Rather than serving as …

Empowering Women: Understanding Neurological Changes In The Aging Brain, Joy Mckenzie

InnovateHER Meeting 2026

Women tend to have more neurological changes than men as they age starting in their mid-30s (Mosconi, 2024). While aging is a natural process, the neurological changes can impact a woman’s personal and professional quality of life (Faubion et al., 2023; Gravini, 2023). For years, women’s neurological symptoms have been ignored by being told that their experiences are normal and just a part of life (Haver, 2025). That narrative is starting to shift with the increased awareness of changes specific to women. There are resources to assess cognitive changes such as memory, processing speed, and word finding and strategies to …

Rhythms Of Hippocampal Function And Memory After Moderate Prenatal Alcohol Exposure, Lilliana May Sanchez

Psychology ETDs

Fetal Alcohol Spectrum Disorders involve morphologic and neurobiological abnormalities in offspring subjected to prenatal alcohol exposure. Although not as well studied as high exposure, moderate prenatal alcohol exposure represents the most common and undetected form in humans. While learning and memory deficits have been well characterized at the behavioral level in humans with Fetal Alcohol Spectrum Disorders and in animal models of moderate prenatal alcohol exposure, few studies have determined the circuit or systems level mechanisms of the behavioral deficits. A complete understanding of the neural bases of memory deficits after moderate prenatal alcohol exposure is needed to ultimately identify …

Exploring The Biological Basis For Exercise Neuroprotection In Parkinson’S Disease: A Cross-Sectional Study Of Exercise And Physical Activity On Inflammatory Cytokines And Neurotrophins, Leah Isabelle P. Alegre, Jacob M. Brewer, Adeline Florschutz, Kate E. Hamiltonthompson

UNLV Theses, Dissertations, Professional Papers, and Capstones

Regular exercise and physical therapy are known to increase production of neurotrophins, including brain-derived neurotrophic factor (BDNF), and anti-inflammatory cytokines. These changes combine to theoretically protect and slow the progressive loss of neurons in Parkinson’s disease (PD). The purpose of this study was to examine the effect of exercise and physical activity on various anti-inflammatory and pro-inflammatory cytokines and neurotrophins in people with PD (PwP). This was a cross-sectional design involving PwP (n=37), aged 43-85 years, who participated in two 30-minute bouts of exercise (with brief rest breaks during and pre/post blood draws) separated by a week. Measures collected prior …

Effectiveness Of Cognitive Stimulation Therapy On The Quality Of Life Of Adults With Dementia: A Secondary Analysis, Evelyn Airam

UNLV Theses, Dissertations, Professional Papers, and Capstones

This secondary analysis study evaluated the effectiveness of Cognitive Stimulation Therapy (CST) on quality of life (QoL), depressive symptoms, and cognitive function in 108 community-dwelling older adults with cognitive impairments, including dementia. Outcomes involved Quality of Life (QoL) measured by the Quality of Life in Alzheimer’s Disease (QoL-AD), symptoms of depression by the Cornell Scale for Depression in Dementia (CSDD), and cognitive function using the Saint Louis University Mental Status (SLUMS). After the CST, significant improvements were observed in QoL (p = .004), depressive symptoms (p = .002), and cognitive function (p < .001), with small effect sizes. Additionally, a significant interaction between sex and dementia diagnosis status was found in predicting cognitive changes, suggesting that the relationship between dementia diagnosis and cognitive improvement differs by sex. No between-group differences were found for QoL or depression. Findings support CST as a multidimensional, non-pharmacological intervention that improves cognitive, psychological, and social outcomes. Although effects were small, consistent improvements are clinically meaningful given the progressive nature of dementia. This study extends existing literature by demonstrating CST’s effectiveness in a community-based setting and reinforces its alignment with occupational therapy’s emphasis on participation and holistic care. Results highlight the need for early intervention and expanded access to CST programs to enhance quality of life in this population.

Stromal Interaction Molecule (Stim) Proteins In Microglia And The Impact On Store-Operated Calcium Entry (Soce) And Spinal Cord Injury Recovery, Norah G. Hill

College of Arts & Sciences Senior Theses

In spinal cord injury (SCI), worsening functional outcomes are largely because of secondary injury processes and prolonged chronic inflammation. A major contributor of secondary injury is overload of intracellular calcium, causing neuronal overexcitation and persistent inflammatory responses. One of the primary mediators of calcium entry into the cell is store-operated calcium entry (SOCE). In SOCE, sensors detecting calcium depletion from the endoplasmic reticulum stores are called STIM proteins (1-2). When calcium is low in the cell, STIM proteins will activate Orai channels to open, allowing for the influx of calcium into the cell. The purpose of this study was to …

Novel Biomarker Discovery In Multiple Sclerosis, Manisha Gangasani

Honors Theses

Multiple Sclerosis (MS) is a chronic neuroinflammatory disorder affecting the brain, spinal cord, and optic nerve. Patients experience cognitive, motor, autonomic, and emotional symptoms that often overlap with other neurological conditions, making early diagnosis challenging. Current diagnostic criteria require evidence of lesions with dissemination in time and space. Racial disparities in MS outcomes are well documented, with Black individuals often exhibiting greater disease severity, higher relapse rates, and increased disability compared to White individuals. These differences likely reflect a combination of genetic, biological, environmental, and healthcare access factors, underscoring the need to improve early diagnosis and reduce inequities in care. …

Eeg Studies Of Pre-Stimulus Activity During Turn-Taking In Naturalistic Conversation, Seyedmohamadreza Manzourolajdad

Student Works (2020-2029)

This study integrates conversational analysis principles and neural activity to investigate natural cognition and examine event-related brain changes. A wireless electroencephalography (EEG) device was used in an ecological validity setting to analyse pre-stimulus brain activity preceding conversational turns. This study aims to identify aspects of the conversation that reflect its naturalness in the aspect of listening and the corresponding brain activity by analysing the signals before and after a turn in a conversation. This research contributes to an ecologically valid understanding of natural conversation as a social action that enables seamless communication. Seven Malaysian participants (aged 19–22, M=20.46) engaged in …

Protocol For Inducing Focal Striatal Stroke In Mice Using Photothrombosis, Bridget R. Boyle, Eileen Collyer, Andrea P. Berghella, Elena Blanco-Suarez

Department of Neuroscience Faculty Papers

Here, we present a protocol for inducing focal striatal stroke in mice using photothrombosis. We describe steps for photothrombotic striatal surgery, magnetic resonance imaging, open field behavioral assessment of stroke-induced motor deficits, and post-stroke monitoring. We then detail procedures for tissue collection and immunofluorescence. This protocol provides a standardized approach for consistently modeling striatal stroke in mice, enabling mechanistic studies and preclinical therapeutic testing.

Hsp90 Inhibitor In Reducing Integrated Stress Response In An Experimental Mouse Model Of Spinal Cord Injury, Yousef Abozaid, Aditya Sarkar, Lukasz P. Slomnicki, Michal Hetman

The Cardinal Edge

Spinal cord injury (SCI) initiates a complex cascade of molecular events, including protein misfolding and neuroinflammation, contributing to neural damage and impaired functional recovery. Heat Shock Protein 90 (HSP90), a critical molecular chaperone involved in cellular stress responses, emerges as a promising therapeutic target to mitigate secondary damage after SCI. This study was designed to validate the in-vivo effects of different doses of HSP90 inhibitor, HSP990-i, administered acutely after moderate T9 SCI mouse model. The level of HSP70 protein level is measured through western blot from the injury epicenter. Adult mice underwent experimental contusive SCI at the T9 level, followed …

Disrupted Nuclear Function And Nucleocytoplasmic Transport In Parkinson’S Disease, Ichiro M. Matoba

The Cardinal Edge

No abstract provided.

The Role Of Top-Down Appetite Self-Regulation In The Development Of Healthy Eating Behaviors Among Children: A Narrative Review And Socialization Framework, David J Bridgett, Sheryl O Hughes, Matthew Broussard, Daniela Mccourt, Christina M Croce, Jennifer O Fisher

Faculty, Staff and Students Publications

Appetite self-regulation (ASR) among children is thought to have a fundamental role in shaping the development of healthy eating behaviors, dietary intake, and growth during childhood. Parallel to developmental frameworks for understanding "general" self-regulation among children, ASR has been described as involving children's use of "top-down" cognitive processes to moderate "bottom-up" biological drives around food approach and avoidance in the interest of achieving desired eating behaviors or outcomes. Whereas bottom-up ASR processes during early childhood are well characterized, particularly in the context of dysregulation and obesity risk, the role of top-down ASR processes in the development of healthy eating behaviors …

Integrated Proteomics To Understand The Role Of Neuritin-1 (Nrn1) As A Molecular Mediator Of Synaptic Resilience In Alzheimer’S Disease, Derian Pugh

ETDs from 2020-2029

Alzheimer’s disease (AD) is the leading cause of dementia in adults over the age of 65, and currently affects approximately 6.9 million people in the United States. By 2060, the number of people age 65 and older with AD is projected to reach 13.8 million, barring the development of disease-altering therapies to prevent, slow or cure AD. Thus, there is a need for progress in the understanding of AD pathophysiology, as well as in the development of diagnostic and therapeutic interventions. Approximately one-third of individuals without dementia at the time of death are found to harbor high levels of amyloid-beta …

Genome-Wide Association Study Identifies Novel Variants In Olfactory, Vitamin A, Vitamin B, And Cadherin Pathways Associated With Learning And Memory, Lloyd N. Hopkins, Nesli Avgan, Heidi G. Sutherland, Francesca E. Fernandez, Emma M. Knowles, Larisa M. Haupt, John Blangero, David C. Glahn, David H. K. Shum, Rod A. Lea, Lyn R. Griffiths

Human Genetics Publications

Learning and memory, as fundamental components of human cognition, are heritable traits that are highly variable between individuals and within populations. Investigation into the genetic basis of cognition is a prominent area of research, with genetic associations being previously reported for a wide range of cognitive phenotypes. Here we utilise a genome-wide association study (GWAS) approach to evaluate the contribution of genetic variation to learning and memory phenotypes in a comprehensively phenotyped, well-characterised, healthy, and unrelated cohort of individuals (n = 613). Cognitive phenotypes were assessed using nine comprehensive test batteries consisting of twenty-one cognitive performance assessments including IQ, five …

From Fog To Function: An Occupational Therapist's Guide To Evaluating And Treating Cancer-Related Cognitive Impairments, Lauren E. Toner

Entry-Level Occupational Therapy Doctorate - Doctoral Capstone Symposium

Cancer – related cognitive impairment (CRCI) is a common side effect of cancer treatment that interferes with cancer survivors’ occupational performance, independence, and quality of life. Despite its high prevalence, CRCI remains under recognized and inconsistently addressed within oncology care. About 70% of individuals diagnosed with cancer report cognitive changes during or after treatment, yet many do not receive treatment. Occupational therapists are clinically trained to evaluate and treat functional cognition, activities of daily activities, instrumental activities of daily living, and client centered goals, positioning them as key providers in addressing CRCI. However, limited occupational therapy specific resources have hindered …

35 Individuals With Huwe1-Related Neurodevelopmental Disorder And Suggested Clinical Evaluations, Mindy H. Li, Deziree L. Coleman, Kelsey Hogan, Danielle Luz, Lindsay Bhandari, Newell Belnap, Tiffany Busa, Charles Coutton, Klaus Dieterich, Svetlana Gorokhova, Clara Hildebrandt, Rachel Logan, Milena Mariani, Manuela Morleo, Vincenzo Nigro, John Pappas, Rachel Rabin, Kelly Schoch, Angelo Selicorni, Vandana Shashi, Rebecca Spillman, Jennifer Sullivan, Charlotte Tardy, Samantha A. Schrier Vergano, Brock Grill, Kristin Baranano

Department of Pediatrics Faculty Publications

HUWE1 (HECT, UBA, and WWE Domain Containing E3 Ubiquitin Protein Ligase1, OMIM 300697), located at Xp11.22, encodes a ubiquitin ligase that is highly conserved across species. Genetic variants in HUWE1 described in multiple independent studies cause X-linked intellectual disability, including in the patients identified by Juberg, Marsidi, and Brooks. This report describes 35 additional cases of individuals with variants in HUWE1 and suggested guidelines for clinical management. Our study includes several female cases, which have not been widely reported previously. Our findings confirm earlier reported clinical features including developmental delay, autism, hypotonia, short stature, and dysmorphic facial features as well …

The Effects Of Stress-Related Hormones On Excitatory Synapse Formation, Autumn C. Garvey

Honors Undergraduate Theses

Stress profoundly influences brain function through neuromodulatory hormones that regulate synaptic plasticity, yet how temporal patterns of hormone exposure shape excitatory synapse formation remains poorly understood. This study investigates how exposure to stress hormones, norepinephrine and cortisol, affects excitatory synapse development. While existing research primarily compares concentration models, real-world stress occurs in variable patterns that may produce distinct neural outcomes. To address this gap, differentiated Neuro2A neuronal cells are exposed to norepinephrine or cortisol under a continuous treatment paradigm designed to model chronic stress conditions. Following treatment, immunofluorescence imaging is utilized to quantify excitatory synapse formation through analysis of presynaptic …

Exploring Anticholinergic Neurotoxicity: Diphenhydramine's Impact On Neuro-2a Cell Morphology, Expression, And Viability, Jordan B. Mcintyre

Honors Undergraduate Theses

Anticholinergic medications, such as diphenhydramine (commonly known as Benadryl), are increasingly recognized for their association with cognitive impairment and neurodegenerative disease. These medications, which inhibit the action of acetylcholine, a neurotransmitter essential for the formation and utilization of the central and peripheral nervous system, have been implicated in conditions such as dementia and may impact fundamental cellular processes like neurogenesis and cell proliferation. This study investigates the effects of diphenhydramine on neurogenesis when introduced to Neuro-2a cells during differentiation. For all studies cells were plated on coverslips or in 6-well plates with differentiation media containing 0 ng/mL, 50 ng/mL, …

Acute And Chronic Effects Of Neuroinflammation On Hippocampus And Anterior Cingulate Cortex Network Dynamics, Lauren A. Crew

UNLV Theses, Dissertations, Professional Papers, and Capstones

Neuroinflammation has emerged as a critical modulator of cognitive function and neural circuit dynamics, yet the distinct contributions of acute and chronic neuroinflammation to brain function remain poorly defined. This dissertation examines how inflammation independently alters large-scale neural activity and behavior, focusing on interactions between the hippocampus (HPC) and anterior cingulate cortex (ACC), regions essential for memory and executive processes. Using in vivo electrophysiological techniques in a rodent model, this study compares the effects of short-term (acute) and prolonged (chronic) neuroinflammatory states, induced via Poly I:C, on neural oscillations, regional coherence, and spatial coding. Findings reveal that even transient inflammation …

Spike Timing Depended Plasticity Produces Unsupervised Learning Of Synergistic Muscle Feedback In A Synthetical Neural Network, Mark Allen Pupkiewicz

Dissertations and Theses

This study investigates how type Ia feedback from muscle spindles can be organized into groups representing agonistic muscle pairs through Spike Timing Dependent Plasticity (STDP). A single degree of freedom joint is actuated with four biologically modeled muscles forming two agonistic pairs. In order to emulate the sensory dynamics of biological muscle spindles, sensors in the model record the active length and velocity states of each muscle, the two primary factors eliciting type Ia afferent responses. In biological networks, synapses from Ia sensory neurons frequently activate interneurons representing agonistic muscle sources. This research investigates whether this organization can emerge in …

Protein-Protein Interaction–Interfering Peptide Rescues Dysregulated Nmda Receptor Signaling, Robert E. Featherstone, Hongbin Li, Ameet S. Sengar, Karin E. Borgmann-Winter, Olya Melnychenko, Lindsey M. Crown, Ray L. Gifford, Felix Amirfathi, Anamika Banerjee, Aivi Tran, Krishna Parekh, Margaret Heller, Wenyu Zhang, Robert J. Gallop, Adam D. Marc, Pragya Komal, Michael W. Salter, Steven J. Siegel, Chang-Gyu Hahn

Farber Institute for Neuroscience Faculty Papers

The complex and heterogeneous genetic architecture of neuropsychiatric illnesses compels us to look beyond individual risk genes for therapeutic strategies and target the interactive dynamics and convergence of their protein products. A mechanistic substrate for convergence of synaptic neuropsychiatric risk genes are protein-protein interactions (PPIs) in the N-methyl-D-aspartate receptor (NMDAR) complex. NMDAR hypofunction in schizophrenia is associated with hypoactivity of Src kinase, resulting from convergent alterations in PPIs of Src with its partners. Of these, the association of Src with PSD-95, which inhibits the activity of this kinase in the NMDAR complex, is known to be increased in schizophrenia. Here, …

Capsinoids, Non-Pungent Trpv1 Agonists, Induce A Mild Hypothermia That Provides Short- And Long-Term Neuroprotection After Ischemic Stroke, Alexander Andersohn, Alexander Andersohn

Dissertations and Theses (Open Access)

Therapeutic hypothermia (TH) has demonstrated neuroprotection in instances of cardiac arrest and neonatal hypoxia/ischemia but faces different challenges in application to stroke due to the activation of cold defense mechanisms in conscious patients. This dissertation examines the efficacy and specificity of capsinoids (a purified mixture of capsiate and dihydrocapsiate) to induce a sustained mild hypothermia in conscious mice that is neuroprotective after stroke. Capsinoids function as TRPV1 agonists. However, unlike capsaicin, capsinoids are vulnerable to esterase-mediated breakdown, thus significantly restricting their action to the site of delivery. We showed that capsinoids delivered intraperitoneally (IP) to mice induced a TRPV1-dependent drop …

Improved Model For Neurodegeneration In C. Elegans, Jean-Pierre Arditi

Graduate Theses and Dissertations (2019 - present)

During Alzheimer's disease (AD), insoluble amyloid beta (AP) peptides accumulate to form extracellular aggregates (plaques). The direct cause of neuronal dysfunction observed in AD has been broadly investigated. The amyloid hypothesis states that AP plaques are neurotoxic, but recent studies support the AP oligomer hypothesis, which states that intracellular AP (iAP) is neurotoxic. To test this hypothesis, I used CRISPR-Cas9 gene editing to generate two transgenic Caenorhabditis elegans (C. elegans) strains. I generated a strain (RSLl 11) using the rab-3 promoter to co-express GFP in neurons, which showed no gross behavioral changes but had a 50% reduced egglaying rate. RSLl …

Rebound Bursting Selectively Enables Fast Dynamics In Dopamine Midbrain Neurons Projecting To The Dorsolateral Striatum, Strahinja Stojanovic, Christopher J. Knowlton, Richard Egger-Mackrodt, Johanna Mankel, Josef Shin, Stephan Lammel, Carmen C. Canavier, Jochen Roeper

School of Graduate Studies Faculty Publications

Dopamine (DA) midbrain neurons are involved in a wide array of key brain functions including movement control and reward-based learning. They are also critical for major brain disorders such as Parkinson's disease or schizophrenia. DA neurons projecting to distinct striatal territories are diverse with regard to their molecular makeup and cellular physiology, which are likely to contribute to the observed differences in temporal DA dynamics. Among these regions, the dorsolateral striatum (DLS) displays the fastest DA dynamics, which might control the moment-to-moment vigor and variability of voluntary movements. However, the underlying mechanisms for these DLS-specific fast DA fluctuations are unresolved. …

Er Stress Tolerance Is Regulated By Copper-Dependent Perk Kinase Activity., Sarah E. Bond Newton, Xinglong Shi, Noah R. Beratan, Julia Perhacs, Jitendra K. Arya, Margaret K. Bond, Tali Gidalevitz, Cagla Akay-Espinoza, Donita C. Brady, Kelly L. Jordan-Sciutto

Farber Institute for Neuroscience Faculty Papers

Pancreatic/PKR-like endoplasmic reticulum (ER) kinase (PERK) is a kinase that, in response to ER stress, mediates dual homeostatic and pro-apoptotic signaling. Thus, intricate regulation is required for physiological function. Attempts to modulate PERK activity have shown that the determinants of adaptive vs. maladaptive signaling remain ambiguous. Here, with purified protein, we provide evidence that PERK binds copper, identifies residues required for interaction, and demonstrates that copper is necessary for kinase activity. Furthermore, cellular PERK activity can be modulated via copper availability, and this regulatory relationship can be manipulated to dictate ER stress tolerance. Critically, these phenomena translate to phenotypes in …